Article

Association of the Vitamin D Metabolism Gene CYP24A1 With Coronary Artery Calcification

Division of Endocrinology, University of Maryland School of Medicine, Baltimore, Md 21201, USA.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 6). 12/2010; 30(12):2648-54. DOI: 10.1161/ATVBAHA.110.211805
Source: PubMed

ABSTRACT

The vitamin D endocrine system is essential for calcium homeostasis, and low levels of vitamin D metabolites have been associated with cardiovascular disease risk. We hypothesized that DNA sequence variation in genes regulating vitamin D metabolism and signaling pathways might influence variation in coronary artery calcification (CAC).
We genotyped single-nucleotide polymorphisms (SNPs) in GC, CYP27B1, CYP24A1, and VDR and tested their association with CAC quantity, as measured by electron beam computed tomography. Initial association studies were carried out in a discovery sample comprising 697 Amish subjects, and SNPs nominally associated with CAC quantity (4 SNPs in CYP24A1, P=0.008 to 0.00003) were then tested for association with CAC quantity in 2 independent cohorts of subjects of white European ancestry (Genetic Epidemiology Network of Arteriopathy study [n=916] and the Penn Coronary Artery Calcification sample [n=2061]). One of the 4 SNPs, rs2762939, was associated with CAC quantity in both the Genetic Epidemiology Network of Arteriopathy (P=0.007) and Penn Coronary Artery Calcification (P=0.01) studies. In all 3 populations, the rs2762939 C allele was associated with lower CAC quantity. Metaanalysis for the association of this SNP with CAC quantity across all 3 studies yielded a P value of 2.9×10(-6).
A common SNP in the CYP24A1 gene was associated with CAC quantity in 3 independent populations. This result suggests a role for vitamin D metabolism in the development of CAC quantity.

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    • "Despite some significant associations between certain SNPs and cvD and/or its risk factors, the majority of the studies reported a lack of significant findings (Shen et al. 2010; Jorde et al. 2012a; Kühn et al. 2013; wilke et al. 2009; li et al. 2013; Trummer et al. 2013). This is in line with data from patients with hereditary 1,25(OH)2D-resistant rickets (HvDRR) who did not exhibit major cardiovascular pathologies (Tiosano et al. 2011). "
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    • "antiproliferative , prodifferentiative and immunomodulatory actions [2]), and vitamin D receptors (VDRs) are present in many cell types, including vascular endothelial cells, smooth muscle cells, cardiomyocytes , pancreatic beta-cells, immune cells and osteoblasts Accordingly, vitamin D deficiency has been implicated in conditions such as type-1 and type-2 diabetes (T2D), cardiovascular disease (CVD), multiple sclerosis and cancer [3e6] as well as in promoting multiple cardiovascular risk factors such as obesity, dyslipoproteinemia and hypertension [5]. Associations have also been demonstrated of vitamin D metabolites [7] [8] and the vitamin D metabolism gene CYP24A1 [9] with coronary artery calcification, a measure of subclinical coronary atherosclerosis and predictor of CVD. "

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    • "antiproliferative , prodifferentiative and immunomodulatory actions [2]), and vitamin D receptors (VDRs) are present in many cell types, including vascular endothelial cells, smooth muscle cells, cardiomyocytes , pancreatic beta-cells, immune cells and osteoblasts Accordingly, vitamin D deficiency has been implicated in conditions such as type-1 and type-2 diabetes (T2D), cardiovascular disease (CVD), multiple sclerosis and cancer [3e6] as well as in promoting multiple cardiovascular risk factors such as obesity, dyslipoproteinemia and hypertension [5]. Associations have also been demonstrated of vitamin D metabolites [7] [8] and the vitamin D metabolism gene CYP24A1 [9] with coronary artery calcification, a measure of subclinical coronary atherosclerosis and predictor of CVD. "
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